quarta-feira, janeiro 30, 2019

‘...the strength of the thread does not reside in the fact that some one fibre runs through its whole length, but in the overlapping of many fibres’ – Ludwig Wittgenstein.

Think of the number of scenarios in which truth matters in science. We care to know whether increased CO2 emission levels cause climate change, and how fast. We care to know whether smoking tobacco increases the risk of lung cancer. We care to know whether poor diet exposes children to the risk of developing obesity, or whether forecasts of economic growth are correct. Truth in science is not esoteric dilly-dallying. It shapes climate science, medicine, public health, the economy and many other worldly endeavours.

That truth matters to science is hardly news. For a long time, people have looked to science for truths about the world. The Scientific Revolution was nothing if not the triumph of Galileo’s scientific truth – hard-won through his telescopic observations – over centuries of dogma about the geocentric system. With its system of epicycles and deferents, Ptolemaic astronomy was at once sophisticated and false. It served to, at best, ‘save the appearances’ about how planets seemed to move in the sky. It did not tell the truth about planetary motion until the discovery of the Copernican explanation. Or consider the Chemical Revolution at the end of the 18th century. We no longer, after all, believe in phlogiston – the fictional imponderable fluid that Georg Ernst Stahl, Joseph Priestley and other natural philosophers at the time believed to be at work in combustion and calcination phenomena. Antoine Lavoisier’s scientific truth about oxygen prevailed over false beliefs about phlogiston.

The main actors of these scientific revolutions often fostered this way of thinking about science as an enquiry leading to the inevitable triumph of truth over past errors. Two centuries after Galileo’s successful defence of the heliocentric system, this idea of the course of scientific truth continued to inspire philosophers. In his Cours de philosophie positive (1830-42), Auguste Comte saw the evolution of human knowledge in three main stages: ‘the Theological, or fictitious; the Metaphysical, or abstract; and the Scientific, or positive’. In the ‘positive’, the third and last stage, ‘an explanation of facts is simply the establishment of a connection between single phenomena and some general facts, the number of which continually diminishes with the progress of science’.

Comte’s positivism was soon decontextualised from its political and social context (after all, Comte started his career working for the social theorist Henri de Saint-Simon, and positivism was inspired by the Industrial Revolution). By the end of the 19th century (and in its early 20th-century reappearance, which I do not have the space to discuss here), the word ‘positivism’ had become – to the ears of many – synonymous with an unfailing optimism in the power of science and technology, and their steady progress toward truth.

In some scientific quarters, this Comtean notion of how science evolves and progresses remains common currency. But philosophers of science, over the past half-century, have turned against the representation of science as a ceaseless forward march toward truth. It is just not how science works, how it moves through history. It flies in the face of the wonderful and subtle historical nuances of how scientific revolutions have in fact occurred. It does not accommodate how some of the greatest scientific minds held dearly to some false beliefs. It wilfully ignores the many voices, disagreements and controversies through which scientific knowledge has often advanced and progressed over time. Simple faith in the ‘Whiggish’ narrative of science naively presumes that progress is marked by some cumulative acquisition of ‘more true beliefs’.

However, many (and legitimate in their own right) criticisms against this naive view of science have committed a similar mistake. They have offered a portrait of science purged of any commitment to truth. They see truth as an inconvenient and disposable feature of science. Fraught as the ideal and pursuit of truth is with tendencies to petty doctrinairism, it is nonetheless a mistake to try to purge it. The fallacy of positivist philosophy was to think of science as coming in stages of some sort, or following a particular path, or historical cycles. The anti-truth trend in the philosophy of science has often ended up repeating this same misstep. It is important to move beyond the sterile dichotomy between the old (quasi-positivist) view of truth in science and the rival anti-truth trend of recent decades.

terça-feira, janeiro 29, 2019

Young inner core inferred from Ediacaran ultra-low geomagnetic field intensity

Richard K. Bono, John A. Tarduno, Francis Nimmo & Rory D. Cottrell

Nature Geoscience volume 12, pages143–147 (2019)

Source/Fonte: NASA

Abstract

An enduring mystery about Earth has been the age of its solid inner core. Plausible yet contrasting core thermal conductivity values lead to inner core growth initiation ages that span 2 billion years, from ~0.5 to >2.5 billion years ago. Palaeomagnetic data provide a direct probe of past core conditions, but heretofore field strength data were lacking for the youngest predicted inner core onset ages. Here we present palaeointensity data from the Ediacaran (~565 million years old) Sept-Îles intrusive suite measured on single plagioclase and clinopyroxene crystals that hosted single-domain magnetic inclusions. These data indicate a time-averaged dipole moment of ~0.7 × 1022 A m2, the lowest value yet reported for the geodynamo from extant rocks and more than ten times smaller than the strength of the present-day field. Palaeomagnetic directional studies of these crystals define two polarities with an unusually high angular dispersion (S = ~26°) at a low latitude. Together with 14 other directional data sets that suggest a hyper-reversal frequency, these extraordinary low field strengths suggest an anomalous field behaviour, consistent with predictions of geodynamo simulations, high thermal conductivities and an Ediacaran onset age of inner core growth.

Acknowledgements

We thank G. Kloc for the sample preparation, B. L. McIntyre and R. Wiegandt for the electron microscope analyses and T. Zhou for magnetic hysteresis measurements. This work was supported by the National Science Foundation (grant nos EAR1520681 and EAR1656348 to J.A.T.).

Department of Earth and Planetary Sciences, University of California, Santa Cruz, CA, USA

Francis Nimmo

Contributions

J.A.T. and R.K.B. conducted the field studies. R.K.B. conducted the palaeomagnetic measurements on the feldspars and R.D.C. measured clinopyroxenes; both data sets were analysed by R.K.B., R.D.C. and J.A.T. Electron microscope analyses were conducted by J.A.T. Core thermal conductivity models were provided by F.N. All the authors participated in the writing of the manuscript. J.A.T. conceived and supervised the study. We thank J. Feinberg for helpful comments.

Theories of a pre-RNA world suggest that glycolonitrile (HOCH2CN) is a key species in the process of ribonucleotide assembly, which is considered as a molecular precursor of nucleic acids. In this Letter, we report the first detection of this pre-biotic molecule in the interstellar medium by using ALMA data obtained at frequencies between 86.5 GHz and 266.5 GHz toward the Solar-type protostar IRAS16293–2422 B. A total of 15 unblended transitions of HOCH2CN were identified. Our analysis indicates the presence of a cold (Tex = 24 ± 8 K) and a warm (Tex = 158 ± 38 K) component meaning that this molecule is present in both the inner hot corino and the outer cold envelope of IRAS16293 B. The relative abundance with respect to H2 is (6.5 ± 0.6) × 10−11 and ≥(6 ± 2) × 10−10 for the warm and cold components, respectively. Our chemical modelling seems to underproduce the observed abundance for both the warm and cold component under various values of the cosmic ray ionization rate (ζ). Key gas phase routes for the formation of this molecule might be missing in our chemical network.

The CRISPR-Cas systems of bacterial and archaeal adaptive immunity have become a household name among biologists and even the general public thanks to the unprecedented success of the new generation of genome editing tools utilizing Cas proteins. However, the fundamental biological features of CRISPR-Cas are of no lesser interest and have major impacts on our understanding of the evolution of antivirus defense, host-parasite coevolution, self versus non-self discrimination and mechanisms of adaptation. CRISPR-Cas systems present the best known case in point for Lamarckian evolution, i.e. generation of heritable, adaptive genomic changes in response to encounters with external factors, in this case, foreign nucleic acids. CRISPR-Cas systems employ multiple mechanisms of self versus non-self discrimination but, as is the case with immune systems in general, are nevertheless costly because autoimmunity cannot be eliminated completely. In addition to the autoimmunity, the fitness cost of CRISPR-Cas systems appears to be determined by their inhibitory effect on horizontal gene transfer, curtailing evolutionary innovation. Hence the dynamic evolution of CRISPR-Cas loci that are frequently lost and (re)acquired by archaea and bacteria. Another fundamental biological feature of CRISPR-Cas is its intimate connection with programmed cell death and dormancy induction in microbes. In this and, possibly, other immune systems, active immune response appears to be coupled to a different form of defense, namely, “altruistic” shutdown of cellular functions resulting in protection of neighboring cells. Finally, analysis of the evolutionary connections of Cas proteins reveals multiple contributions of mobile genetic elements (MGE) to the origin of various components of CRISPR-Cas systems, furthermore, different biological systems that function by genome manipulation appear to have evolved convergently from unrelated MGE. The shared features of adaptive defense systems and MGE, namely the ability to recognize and cleave unique sites in genomes, make them ideal candidates for genome editing and engineering tools.

Eugene Koonin says the CRISPR-Cas system cannot be fitted within Darwinian categories:

"With regard to general aspects of evolution, CRISPR-Cas systems perfectly illustrate another key point, namely the fundamental difference between the Darwinian (selection) and Wrightian (genetic drift) modes of evolution, on the one hand, and the Lamarckian mode, on the other hand. Darwinian evolution that is based on negative and positive selection acting on random mutations as well as genetic drift (Wrightian evolution) are intrinsic features of replicator systems which are inherently error-prone. These mechanisms have been operating since the origin of the first replicators which can be considered equivalent to the origin of life (Koonin 2011). In contrast, Lamarckian evolution requires elaborate machinery for 'natural genome engineering', such as the CRISPR-Cas systems.”

a) Chemical structures of TAP and CyCo6, the hexad structure formed by H‐bonding of three monomers of each, and an illustration of helically twisted stacked hexads. b) Circular dichroism spectra of a TAP‐CyCo6 sample (30 mm in each monomer) acquired at temperatures ranging from 5 to 40 °C. c) Circular dichroism spectra of 40 independently made samples containing TAP and CyCo6 (30 mm in each monomer) acquired at 20 °C.

Abstract

Aqueous solutions of the achiral, monomeric, nucleobase mimics (2,4,6‐triaminopyrimidine, TAP, and a cyanuric acid derivative, CyCo6) spontaneously assemble into macroscopic homochiral domains of supramolecular polymers. These assemblies exhibit a high degree of chiral amplification. Addition of a small quantity of one handedness of a chiral derivative of CyCo6 generates exclusively homochiral structures. This system exhibits the highest reported degree of chiral amplification for dynamic helical polymers or supramolecular helices. Significantly, homochiral polymers comprised of hexameric rosettes with structural features that resemble nucleic acids are formed from mixtures of cyanuric acid (Cy) and ribonucleotides (l‐, d‐pTARC) that arise spontaneously from the reaction of TAP with the sugars. These findings support the hypothesis that nucleic acid homochirality was a result of symmetry breaking at the supramolecular polymer level.

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as https://doi.org/10.1111/evo.13686

Is feeding ecology the main driver of beak diversification in modern birds? Taking a broad‐scale interspecific comparative approach, Navalón et al. (2019) found a relationship between feeding ecology (diet and feeding behavior) and beak morphology (shape and leverage), although much of the observed variation remained unexplained. This low explanatory power may suggest that variation in the multitude of non‐feeding functions of the beak also influences its evolution.

Artist’s impression of the molecules found in a hot molecular core in the Large Magellanic Cloud. [FRIS/Tohoku University; ESO/M. Kornmesser; NASA/ESA/S. Beckwith (STScI)/HUDF Team; Hubble Heritage Team (AURA/STScI)/HEI]

To date, 204 individual molecular species, comprised of 16 different elements, have been detected in the interstellar and circumstellar medium by astronomical observations. These molecules range in size from 2 atoms to 70, and have been detected across the electromagnetic spectrum from centimeter wavelengths to the ultraviolet. This census presents a summary of the first detection of each molecular species, including the observational facility, wavelength range, transitions, and enabling laboratory spectroscopic work, as well as listing tentative and disputed detections. Tables of molecules detected in interstellar ices, external galaxies, protoplanetary disks, and exoplanetary atmospheres are provided. A number of visual representations of these aggregate data are presented and briefly discussed in context.

Adaptive landscapes provide comprehensive overviews of biological phenomena. They reveal, among other things, targets of selection, optimality principles, structural constraints, evolutionary trade-offs and the origins of epistasis. The concept has captivated biologists for nearly a century and yet remains a metaphor. We redefine adaptive landscapes in terms of biological processes rather than descriptive phenomenology. We eschew association studies to focus on the underlying mechanisms that generate emergent properties such as epistasis, dominance, trade-offs and adaptive peaks. We illustrate the utility of landscapes in predicting, among other things, the course of adaptation and the distribution of fitness effects. We abandon aged arguments concerning landscape ruggedness in favor of empirically determining landscape architecture. In so doing, we transform the landscape metaphor into a scientific framework within which causal hypotheses can be tested.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

• Many transcription factors have shape motifs in both in vivo and in vitro data

• Shape motifs may encode specificity that goes beyond the sequence motifs of a TF

Summary

DNA shape adds specificity to sequence motifs but has not been explored systematically outside this context. We hypothesized that DNA-binding proteins (DBPs) preferentially occupy DNA with specific structures (“shape motifs”) regardless of whether or not these correspond to high information content sequence motifs. We present ShapeMF, a Gibbs sampling algorithm that identifies de novo shape motifs. Using binding data from hundreds of in vivo and in vitro experiments, we show that most DBPs have shape motifs and can occupy these in the absence of sequence motifs. This “shape-only binding” is common for many DBPs and in regions co-bound by multiple DBPs. When shape and sequence motifs co-occur, they can be overlapping, flanking, or separated by consistent spacing. Finally, DBPs within the same protein family have different shape motifs, explaining their distinct genome-wide occupancy despite having similar sequence motifs. These results suggest that shape motifs not only complement sequence motifs but also facilitate recognition of DNA beyond conventionally defined sequence motifs.

ACS Editors' Choice - This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License, which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.

Abstract

Folding can bestow macromolecules with various properties, as evident from nature’s proteins. Until now complex folded molecules are the product either of evolution or of an elaborate process of design and synthesis. We now show that molecules that fold in a well-defined architecture of substantial complexity can emerge autonomously and selectively from a simple precursor. Specifically, we have identified a self-synthesizing macrocyclic foldamer with a complex and unprecedented secondary and tertiary structure that constructs itself highly selectively from 15 identical peptide-nucleobase subunits, using a dynamic combinatorial chemistry approach. Folding of the structure drives its synthesis in 95% yield from a mixture of interconverting molecules of different ring sizes in a one-step process. Single-crystal X-ray crystallography and NMR reveal a folding pattern based on an intricate network of noncovalent interactions involving residues spaced apart widely in the linear sequence. These results establish dynamic combinatorial chemistry as a powerful approach to developing synthetic molecules with folding motifs of a complexity that goes well beyond that accessible with current design approaches. The fact that such molecules can form autonomously implies that they may have played a role in the origin of life at earlier stages than previously thought possible.

We present the genome of the moon jellyfish Aurelia, a genome from a cnidarian with a medusa life stage. Our analyses suggest that gene gain and loss in Aurelia is comparable to what has been found in its morphologically simpler relatives—the anthozoan corals and sea anemones. RNA sequencing analysis does not support the hypothesis that taxonomically restricted (orphan) genes play an oversized role in the development of the medusa stage. Instead, genes broadly conserved across animals and eukaryotes play comparable roles throughout the life cycle. All life stages of Aurelia are significantly enriched in the expression of genes that are hypothesized to interact in protein networks found in bilaterian animals. Collectively, our results suggest that increased life cycle complexity in Aurelia does not correlate with an increased number of genes. This leads to two possible evolutionary scenarios: either medusozoans evolved their complex medusa life stage (with concomitant shifts into new ecological niches) primarily by re-working genetic pathways already present in the last common ancestor of cnidarians, or the earliest cnidarians had a medusa life stage, which was subsequently lost in the anthozoans. While we favour the earlier hypothesis, the latter is consistent with growing evidence that many of the earliest animals were more physically complex than previously hypothesized.

Acknowledgements

We thank K. Kosik and N. Nakanishi for their insights during the development of this project; R. Warren for his advice on genome assembly strategy; V. Levesque and the Birch Aquarium at Scripps for providing Aurelia strains; and S. Johnson, D. Le, D. Lam, and A. Hsu for technical assistance. D.A.G. gratefully acknowledges funding from a National Institutes of Health Training Grant in Genomic Analysis and Interpretation (T32HG002536) and a Cordes Postdoctoral Fellowship from the Division of Biology and Biological Engineering at Caltech. This work was also supported by grants from the W.M. Keck Foundation (R.J.G.), the Gordon and Betty Moore Foundation (R.J.G.), the DFG (T.H.), a fellowship from the Uehara Memorial Foundation (T.K.) and the NASA Astrobiology Institute–Foundations of Complex Life: Evolution, Preservation and Detection on Earth and Beyond (D.K.J.).

Division of Biological Sciences, University of California San Diego, La Jolla, CA, USA

Ralph J. Greenspan

Department of Cognitive Science, University of California San Diego, La Jolla, CA, USA

Ralph J. Greenspan

Contributions

R.J.G. and T.K. sequenced and assembled the genome with input from R.E.S. M.R. contributed 100-bp paired-end reads, and D.I. and T.H. provided mate-pair reads with 4-kbp inserts. X.Y. and Y.L. worked on the initial error correction of PacBio reads. D.K.J. and D.A.G. oversaw transcriptome sequencing and assembly. D.A.G. performed downstream analyses of genome annotation with input from T.K., R.J.G., R.E.S. and D.K.J. D.A.G. designed the figures and drafted the manuscript. All authors reviewed and approved the final paper.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to David A. Gold or Takeo Katsuki or Ralph J. Greenspan.

This article considers the main methodological objections against the theory of intelligent design.In general, they claim that it lacks a scientific character and they emphasize that design cannot be detected using scientific tools. The critics focus on showing that intelligent design violates various methodological criteria.In response to these objections, this article examines the methodological claim made by its proponents that the characteristic effects of the designer’s activity do provide a sufficient basis for inferring design. This paper also argues that the procedure of inferring that a certain feature has been designed by a supernatural being does not differ in principle from design-detection procedures in other spheres of research.

The measurement of chirality and its temporal evolution are crucial for the understanding of a large range of biological functions and chemical reactions. Steady-state circular dichroism (CD) is a standard analytical tool for measuring chirality in chemistry and biology. Nevertheless, its push into the ultrafast time domain and in the deep-ultraviolet has remained a challenge, with only some isolated reports of subnanosecond CD. Here, we present a broadband time-resolved CD spectrometer in the deep ultraviolet (UV) spectral range with femtosecond time resolution. The setup employs a photoelastic modulator to achieve shot-to-shot polarization switching of a 20 kHz pulse train of broadband femtosecond deep-UV pulses (250–370 nm). The resulting sequence of alternating left- and right-circularly polarized probe pulses is employed in a pump-probe scheme with shot-to-shot dispersive detection and thus allows for the acquisition of broadband CD spectra of ground- and excited-state species. Through polarization scrambling of the probe pulses prior to detection, artifact-free static and transient CD spectra of enantiopure [Ru(bpy)3]2+ are successfully recorded with a sensitivity of <2 amino-acid="" and="" biological="" broadband="" changes="" chirality="" deep-uv="" detection="" dna="" due="" feasible.="" font="" in="" is="" its="" mdeg="" measurement="" now="" od="" of="" oligomers="" peptides="" residues="" sensitivity="" systems="" the="" to="" ultrafast="" unprecedented="" with="">2>

Predicting evolutionary change poses numerous challenges. Here we take advantage of the model bacterium Pseudomonas fluorescens in which the genotype-to-phenotype map determining evolution of the adaptive ‘wrinkly spreader’ (WS) type is known. We present mathematical descriptions of three necessary regulatory pathways and use these to predict both the rate at which each mutational route is used and the expected mutational targets. To test predictions, mutation rates and targets were determined for each pathway. Unanticipated mutational hotspots caused experimental observations to depart from predictions but additional data led to refined models. A mismatch was observed between the spectra of WS-causing mutations obtained with and without selection due to low fitness of previously undetected WS-causing mutations. Our findings contribute toward the development of mechanistic models for forecasting evolution, highlight current limitations, and draw attention to challenges in predicting locus-specific mutational biases and fitness effects.

Predicting evolution might sound like an impossible task. The immense complexity of biological systems and their interactions with the environment has meant that many biologists have abandoned the idea as a lost cause. But despite this, evolution often repeats itself. This repeatability offers hope for being able to spot in advance how evolution will happen. To make general predictions, it is necessary to understand the mechanisms underlying evolutionary pathways, and studying microbes in the laboratory allows for real-time experiments in evolution.

One of the best studied microbes for experimental evolution is Pseudomonas fluorescens, which repeatedly evolves flattened wrinkled colonies instead of round smooth ones when there is limited oxygen. The underlying molecular pathways that lead to this change have been studied in detail.

Lind et al. developed mathematical models to predict how often the three most common pathways would be used and which genes were most likely to be mutated. After controlling for the effects of natural selection and refining the models to take into account mutation hotspots, Lind et al. were able to accurately predict the genes that would be targeted by mutations.

The findings suggest that biologists need not lose hope when it comes to the goal of predicting evolution. A deep understanding of the molecular mechanisms of evolutionary changes are essential to predicting the mutations that lead to adaptive change. The results are an important first step towards forecasting organisms’ responses to changing conditions in the future. In the short term, this is important for medical issues, including antibiotic resistance, cancer and immune receptors. In the long term, predicting the course of evolution could be essential for survival of life on the planet.

In this article, we review the state-of-the-art results in evolutionary computation and observe that we do not evolve nontrivial software from scratch and with no human intervention. A number of possible explanations are considered, but we conclude that computational complexity of the problem prevents it from being solved as currently attempted. A detailed analysis of necessary and available computational resources is provided to support our findings.

The evolution of body shape is thought to be tightly coupled to changes in regulatory sequences, but specific molecular events associated with major morphological transitions in vertebrates have remained elusive. We identified snake-specific sequence changes within an otherwise highly conserved long-range limb enhancer of Sonic hedgehog (Shh). Transgenic mouse reporter assays revealed that the in vivo activity pattern of the enhancer is conserved across a wide range of vertebrates, including fish, but not in snakes. Genomic substitution of the mouse enhancer with its human or fish ortholog results in normal limb development. In contrast, replacement with snake orthologs caused severe limb reduction. Synthetic restoration of a single transcription factor binding site lost in the snake lineage reinstated full in vivo function to the snake enhancer. Our results demonstrate changes in a regulatory sequence associated with a major body plan transition and highlight the role of enhancers in morphological evolution.